1. Technical Field
The present invention relates to proteins having a hemolytic activity and genes encoding them. More specifically, the present invention relates to novel proteins having the hemolytic activity, a process for producing and the use of the same as well as antibodies for such proteins.
2. Background
The sting injury by the jellyfish in sea bathing has occurred in various parts of the world. The sting injury by Carybdea rastonii or Physalia physalis has also occurred frequently in Japan every year in the season of sea bathing of the summertime. The degree of the symptom by sting differs by species of a jellyfish and the individual differences of patients. The first symptom is dermotoses, such as pain, flare, papule, vesicle and so on in the sting site. In a serious illness, patients may die with generating of hemorrhagic maculae and the necrosis, and also constitutional symptom, such as headache, high fever, nausea, dyspnea, and the fluctuation of a pulse. Although such sting injury is occurring frequently, the determination and pharmacological properties of the toxic components of jellyfish have not been studied intensively. Therefore, the development of medicines for treatment of the sting by the jellyfish is also hardly performed before the present invention.
The studies on the toxic components of Carybdea rastonii have reported by Sato et al., and they found that there are some active substances having physiological activities, such as hemolysis, platelet agglutination, mast cell degranulation, the vessel smoothness muscle contraction, the dermal necrosis, the heart poison and the fatality in the crude extract fractions from the freeze-dried tentacle of Carybdea rastonii. They also examined on the platelet agglutination effect and vessel smoothness muscle contraction effect of the toxic component (Akihiko Sato, “Research on the toxic component of Carybdea rastonii”, The Journal of the Ochanomizu Medico-dental Society, vol. 33, No. 2, 131-151, June, 1985).
On the one hand, since the poison from the nematocyst of a jellyfish was a non-dialyzable high polymer and deactivated by treatment with acid or alkali, or by heating processing, organic solvent processing, protease processing, etc., it was thought that the main components of this poison were proteins.
Moreover, the purification of the protein toxin derived from a jellyfish has also been tried; however, the isolation and the purification of the active components maintaining the hemolytic activity were not performed since the toxin of a jellyfish itself was very easy to be deactivated. Therefore, the physical and chemical properties of the toxin from jellyfish were not known up to now.
The detailed studies on the toxic component of a jellyfish is very important for the development of drugs applying their various physiological activities, in particular, specific hemolytic activity and the platelet agglutination effect.
Therefore, the problems to be solved by the present invention is providing an approach to development of the drugs for treatment of the sting injury by the jellyfish by means of isolating the proteins or peptides having as potent hemolytic activity as possible, in the state where the physiologic activity is retained. The present invention further provides the approach to study similarities on embryology or structure, and the species specificity of the protein having hemolytic activity to evaluate the structure-activity relationship thereof.